Despite the importance of cell-substratum interactions in determining the behavior of normal and neoplastic cells, the proteins responsible for attachment have not yet been identified directly. We have developed a method whereby lactoperoxidase is covalently coupled to polystyrene tissue culture flasks and used to radioiodinate the monolayer cell proteins that come into intimate contact with the lactoperoxidase-polystyrene surface. In the proposed project, this system would be used to label the polypeptides in extracellular material and plasma membranes of attached cells. Lactoperoxidase will also be coupled to various natural extracellular proteins and used to label the membrane and, possibly, the intracellular proteins that interact with it. The labeled polypeptides will be analyzed on exponential gradient SDS-polyacrylamide gels and their localization will be determined by usual fractionation methods. The data thus obtained should reveal the chain of interactions between extracellular, intramembrane and intracellular proteins in normal cells. Disturbances that accompany neoplastic transformation should also be apparent.